We are continuing our studies to determine the role of reactive metabolites of acetaminophen in the pathogenesis of analgesic nephropathy. The pattern of urinary excretion of metabolites has been established for the hamster with the demonstration that 3-sCH3 and 3-SO2CH3 are derived from the eneterohepatic circulation. We can not identify N-OH-APAP in the urine after the administration of APAP, but it does appear after the administration on N-OH-APAP itself. The next step is to determine the renal mechanisms involved in the excretion of N-OH-APAP as well as to document its direct nephrotoxicity in greater detail.